Estudis de regulació i funció dels gens dUCP3 i Pref-1 en teixits adiposos i muscular
Abstract: Mitochondrial uncoupling protein 3 (UCP3) homologous to termogenic UCP1, is mainly expressed in muscular and brown adipose tissues but its physiological function remains unknown. We have carried out gene expression studies in skeletal muscle and adipose tissues of UCP3 knockout mice and we have observed: 1. UCP3 gene deletion in those mice does not impairs oxidative stress related gene expression in skeletal muscle from newborn mice, althought UCP3 gene expression is dramatically induced in wild-type mice during this period. 2. Ageing does not impairs blood parameters neither expression of genes related to oxidative stress and oxidative metabolism in skeletal muscle, brown (BAT) and white (WAT) adipose tissues and liver from knockout mice. Whole genome microarray did not show clear changes in gene expresion. 3. Long term high-fat carbohidrate free diet feeding during agening lead to body weight increase without any change in blood parameters, and a significant increase in UCP3 protein content in skeletal muscle. 4. This diet caused diferential effects on knockout mice: blood ketone bodies increment and impaired expression of genes related to oxidative stress and energetic metabolism. 5. Pref-1 gene is sensitively regulated in adult brown and white fat. BAT and WAT have and oposite role in energy balance. Since Pref-1 has been described as a negative regulator of white adipocyte differenciation, we have studied its biological function and regulation on brown adipocytes and on BAT. 1. Pref-1 gene disruption (Pref-1 knockout mice) impairs BAT morfology and gene expression during its development, consisting on a thermogenic overactivation. This suggest a specific potential repressor rol for Pref-1 compared to WAT differentiation. Nevertheless, these changes do not persist in adult mice under thermogenic stimulus. 2. Unlike WAT, BAT development take place in foetal period, in presence of a high Pref-1 gene expression. 3. In brown adipocytes, Pref-1 gene is positively regulated by C/EBP-beta and specially by C/EBP-delta transcription factors. This fact can explain Pref-1 strong overinduction in BAT from C/EBP-alpha knockout mice which also displays C/EBP-beta and C/EBP-delta overexpression. These results suggest differential rol for C/EBP-delta in brown adipocyte differentiation and gene expression compared to white adipocyte.
Advisor:Villarroya Gombau, Francesc
School:Universitat de Barcelona
Source Type:Master's Thesis
Keywords:bioquímica i biologia molecular fac
Date of Publication:10/26/2007